AB0075 PRESENCE AND EFFECT OF MUSCLE GDF-8 AND GDF-11 IN THE SYNOVIUM OF PATIENTS WITH RHEUMATOID ARTHRITIS
Authors: M. L. Gasparini Vieira, R. T. Pedo, J. Miranda de Souza Silva, M. Farinon, S. Dalmolin, M. Piccoli, M. Dos Santos, B. Bartikoski, R. Cavalheiro Do Espírito Santo, V. Hax, R. Xavier
Journal: Annals of the Rheumatic Diseases (2023)

<h3>Background</h3> Myokines, such as the growth differentiation factor (GDF) 8 and 11, have the function of regulating autocrine and paracrine activities on muscle tissue metabolism. In Rheumatoid Arthritis (RA), there is increased expression of GDF-8 in the synovial membrane compared to osteoarthritis (OA) patients, more specifically by fibroblast-like synoviocytes (FLS). On the other hand, the GDF-11 treatment appears to have a protective effect against the development of experimental arthritis. Therefore, more studies evaluating the serum and synovial membrane levels of the GDF-8 and GDF-11 in RA patients are needed to better define their possible roles in this disease. <h3>Objectives</h3> To evaluate the GDF-8 and GDF-11 in serum and synovial membrane levels in RA patients and to assess their <i>in vitro</i> effect on FLS. <h3>Methods</h3> Patients diagnosed with RA and patients with knee OA with the indication of knee arthrocentesis were included in the study. Disease activity was assessed by Clinical Disease Activity Index (CDAI). The evaluation of serum and synovial fluid levels of GDF-8 and GDF-11 was performed by ELISA. FLS were isolated from the synovial fluid of RA patients, and cell viability was determined in the presence and absence of GDF-8 and GDF-11 (10nM; 20nM and 50nM) for 24h and 48h by the MTT assay. Kolmogorov–Smirnov, Mann-Whitney U and Spearman's correlation tests were performed using SPSS version 20.0 (accepted at p ≤0.05). <h3>Results</h3> As preliminary data, samples from 11 patients with RA and 5 patients with knee OA were evaluated. GDF-8 synovial fluid levels were lower than serum levels in RA patients (p=0.007) and were negatively correlated with disease duration (r=-0.684, p=0.02). GDF-11 levels in synovial fluid were also lower than in serum in RA (p=0.018) and were higher in RA patients than in the OA group (p= 0.052). Furthermore, treatment with different concentrations of GDF-8 and GDF-11 did not affect FLS viability. <h3>Conclusion</h3> In this preliminary research, we found lower GDF-8 and GDF-11 synovial fluid levels than in serum in RA patients and higher GDF-11 serum levels in the RA group compared to the OA group. This result could be related to local compensatory mechanisms against the inflammatory state. <i>In vitro</i>, both GDF-8 and GDF-11 did not induce proliferation or death of FLS, and more studies are undergoing to analyze their impact on the FLS phenotype. Our results contribute to the knowledge about the participation of myokines in the pathogenesis of RA. <h3>References</h3> [1]Dankbar B, Fennen M, Brunert D, Hayer S, Frank S, Wehmeyer C, et al. Myostatin is a direct regulator of osteoclast differentiation and its inhibition reduces inflammatory joint destruction in mice. Nat Med. 2015 Sep 8;21(9):1085–90. [2]Li, W. et al. GDF11 antagonizes TNF-α-induced inflammation and protects against the development of inflammatory arthritis in mice. FASEB Journal, v. 33, n. 3, p. 3317– 3329. <h3>Acknowledgements</h3> Coordenação de Aperfeiçoamento de Pessoal de Nível Superior, CAPES. <h3>Disclosure of Interests</h3> None Declared.